Peripheral Neuropathy
Ralph F. Józefowicz, MD
PN: Definition
• A general term for any disorder affecting
the peripheral nerves.
Symptoms of Neuropathy
• Sensory:
– Dysesthesias in distal extremities
– Pain
– Numbness (stocking-glove)
• Motor:
– Distal>proximal weakness
• Autonomic:
– Orthostatic hypotension
– Impotence
Signs of Neuropathy
• Sensory
– Large fiber loss (vibration, proprioception)
– Small fiber loss (pain, temperature)
• Motor
– Weakness (distal>proximal, extensor>flexor)
– Muscle atrophy
– Flaccid tone
• Reflexes: absent or reduced
• Autonomic: orthostatic hypotension
Classification of Neuropathy
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Etiology
Distribution
Pathology
Modality
Etiology of Neuropathy
• Hereditary
• Toxic/metabolic
– Drugs
– Toxins
• 2° to systemic disease
• Autoimmune
Hereditary
• Charcot-Marie-Tooth disease (HSMN I&II)
• Dejerine-Sottas disease (HSMN III)
• Refsum’s disease (HSMN IV)
Drugs
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Amiodarone
cis-platinum
Dapsone
INH
Phenytoin
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Pyridoxine
Vincristine
Nitrofurantoin
ddI
ddC
Toxins
• Heavy metals
– Hg, Pb, Zn, As
• Ethanol
• Organophosphates
Systemic Diseases
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Diabetes mellitus
Uremia
Porphyria
Pernicious anemia
Amyloidosis
Hypothyroidism
Carcinoma
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Lymphoma
Multiple myeloma
Cryoglobulinemia
Monoclonal gammopathy
Vasculitis (SLE, RA, PAN)
Sarcoidosis
Infection
Diabetes Mellitus
• Symmetric neuropathies
– Sensory>motor polyneuropathy
– Autonomic neuropathy
• Asymmetric neuropathies
– Mononeuropathy multiplex
– Cranial neuropathy
– Truncal radiculopathy
– Amyotrophy
– Entrapment neuropathy
Infections
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Leprosy
Syphilis
HIV
Diphtheria
Autoimmune
• Guillain-Barré syndrome (AIDP)
• Chronic inflammatory demyelinating
polyneuropathy (CIDP)
Distribution
• Symmetrical generalized
– Polyneuropathy
(stocking-glove, dying back neuropathy)
• Multifocal
– Mononeuropathy multiplex
• Focal
– Entrapment neuropathy
Pathology
• Axonopathy:
• Myelinopathy:
• Neuronopathy
most polyneuropathies
GBS, CIDP
– Somatic motor: ALS
– Somatic sensory: carcinoma, Sjögren's
– Autonomic:
hereditary dysautonomia
Modality
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Motor
Sensory
Autonomic
Mixed
Etiology of Peripheral Neuropathies
DANG THERAPIST
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Diabetes
Alcohol
Nutritional
Guillain-Barré
Toxic
Hematologic
Endocrine
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Rheumatologic
Amyloid
Porphyria
Infectious
Sarcoid
Tumor
Diagnostic Studies
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Nerve conduction study
Electromyography
Serum studies
Urine studies
Nerve biopsy
Nerve Conduction Study
• Demyelinating lesions:
– Slowed conduction velocities
– Prolonged terminal latencies
– Dispersion of evoked CMAP
– Conduction block
• Axonal lesions:
– Reduced amplitudes of CMAP and SNAP
Electromyography
• Axonal lesions:
– Acute denervation:
fibrillation potentials
positive waves
– Chronic denervation: large, prolonged CMAP
reduced recruitment
• Demyelinating lesions:
– Reduced recruitment
Serum Studies
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CBC
Chemistry profile
T4, TSH
Vitamin B12 assay
ESR
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ANA
Rheumatoid factor
SPEP
SIEP
RPR
HIV
Urine Studies
• Heavy metal screen
• Porphobilinogen
Nerve Biopsy
(Sural Nerve)
• Only helpful in screening for
– Vasculitis
– Amyloid
– Sarcoid
– Leprosy
Normal Sural Nerve
Trichrome Stain
Chronic Axonal Neuropathy
Trichrome Stain
Vasculitis
H&E Stain
CIDP
Toluidine Blue Stain
Demyelinating Neuropathy
Teased Nerve Fiber Preparation
Treatment of Neuropathies
• Specific treatment
• Treatment of immune-mediated neuropathies
• Symptomatic treatment
Treatment of Immune Mediated
Neuropathies
• Corticosteroids
• Immunosuppressive drugs
– Azathioprine
– Cyclophosphamide
– Mycophenolate
• Plasmapheresis
• IVIg
Symptomatic Treatment
• Tricyclic compounds • Anticonvulsants
– Amitriptyline
– Nortriptyline
– Duloxetine
– Gabapentin
– Pregabilin
• Topicals
– Capsaicin
– Lidocaine patch
Case 1
A 23-year-old, right-handed college student and
summer waitress was well until one month ago when
she developed tingling in both hands, primarily in the
thumb, second and third digits, and worse on the right.
It frequently awoke her from sleep. She occasionally
noted pain in her right forearm. She denied any hand
weakness. No history of neck pain.
She started to work as a waitress 2 months ago. She
had no tingling when waiting on tables or when mowing
the lawn but developed the tingling afterwards.
Case 1 – PMH
Past Medical History: Herniated lumbar disk following a
fall; s/p right L5 laminectomy
Medications: Oral contraceptives
Family History: Unremarkable
Case 1 – Examination
Physical Examination:
• P=108/min; BP=110/80 mm Hg
• Neck ROM full
• Tinel sign negative bilaterally
• Phalen sign positive bilaterally
Neurologic Examination:
• Motor exam: Slight weakness of the right APB muscle
• Sensory exam: normal, including hands and feet
• MSR: 3+ bilaterally, including ankle jerks
• Romberg: negative
Case 1 – Nerve Conductions
Nerve
R median
motor
Terminal
latency
Amplitude
Conduction
Velocity
7.0 msec
3.9 mV
59 m/sec
L median motor 6.2 msec
6.6 mV
55 m/sec
Normal
<4.2 msec
>10 mV
>50 m/sec
R median
sensory
5.0 msec
8.4 μV
L median
sensory
5.3 msec
7.2 μV
Normal
<3.6 msec
>20 μV
Case 1 – Laboratory
• T4
• Free T4
• TSH
23.5 μg/dl
9.68 units
<0.1 mIU/L
Diagnosis?
Carpal Tunnel Syndrome
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Median nerve compression at the wrist
Motor: APB muscle weakness
Sensory: digits 1, 2, 3, lateral digit 4
Pain: wrist, median hand, forearm
Tinel and Phalen signs
EMG and nerve conduction study
Treatment: wrist splints and surgery
The Carpal Tunnel
Case 2
A 56-year-old mechanical engineer was referred for
evaluation of numb toes that came on gradually and
painlessly 12 years ago. The numbness is most
pronounced when he is trying to fall asleep and is made
worse by cold weather; warm weather improves the
sensation in his feet. He has decreased sensation on
the soles of his feet when he is stepping on the pedals
in his car. Walking barefoot produces intense pain. The
numbness has progressed to involve the distal feet.
He denies weakness in his feet, walking difficulty, bowel
or bladder difficulty, sexual dysfunction, or back or neck
pain.
Case 2 – PMH
Past Medical History: Hypertension, meralgia
paresthetica, s/p appendectomy
Medications: captopril, potassium, aspirin
Habits: occasional EtOH, no tobacco
Family History: unremarkable
Case 2 – Examination
Physical examination:
• P=60/min, BP=160/100 mm Hg
• Moderately obese, lipoma over right lateral hip
• Neck and back ROM intact; SLR negative
Neurologic examination:
• Motor: atrophy of EDB muscles in both feet; unable
to fully cock up his toes
• Sensory: reduced pin sensation in toes; absent
vibration and position sense in feet
• Reflexes: absent ankle jerks
Case 2 – Laboratory
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NCS
ANA
Anti DS-DNA
RF
SPEP
Immunofixation
demyelinating neuropathy
≥1:640, speckled
<10
Negative
Normal pattern
Monoclonal IgM lambda protein
Diagnosis?
Distal Polyneuropathy
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Symmetric, distal sensory>motor
“Stocking – glove” neuropathy
“Dying back” neuropathy
Pathology: usually mixed axonal and
demyelinating features
• Various etiologies, including DM,
nutritional deficiency, toxins, metabolic
Case 3
A 70-year-old woman developed numbness in her feet
and upper back pain. The following month she
developed a left Bell's palsy that was treated with a
seven day course of prednisone. She then developed
progressive numbness and pain in her feet and hands
in a stocking-glove distribution. Distal weakness
developed after this. She was treated with amitriptyline
which helped the pain but not the numbness or
weakness. Over the past two weeks her weakness
worsened to the point that she had difficulty walking
because of bilateral foot drop. She was therefore
admitted for further evaluation.
Case 3 – PMH
Past Medical History: Hypertension
Medications: HCTZ, nifedipine, ranitidine, ASA
Case 3 – Examination
Physical Examination:
• P=84/min; BP=140/82 mm Hg; T=37°C
• Grade 2/6 SEM present
Neurologic Examination:
• Motor: unable to stand on heels or toes; grade 4
weakness in biceps, wrist extensors and flexors,
finger flexors and psoas muscles; grade 2 weakness
in interossei and dorsi and plantar flexor muscles
• Sensory: light touch, temperature and pin reduced in
a stocking-glove distribution; vibration and position
sense absent at the toes;
• Reflexes: UE 2+; knees 1+; ankles absent
• Gait: bilateral steppage
Case 3 – Laboratory
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CBC
ESR
ClCr
ANA
RF
Anti DS-DNA
Anti RNP
Anti SM
Anti SSA
Anti SSB
WBC=11.0/mm3; Hct=37%
90 mm/hr
42 ml/min
1:160, homogeneous
Negative
Negative
Negative
Negative
Negative
Negative
Case 3 – Additional Labs
• NCS
• Sural nerve biopsy
Demyelinating neuropathy
Vasculitis
Diagnosis?
Vasculitic Neuropathy
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Due to infarction of vasa nervorum
Usually asymmetric
Involves peripheral nerves, roots, plexi
Typically painful
Etiology: vasculitis, DM
Case 4
A 63-year-old school bus driver noted tingling and
numbness in her limbs two months ago. The tingling
first began in her left arm and leg. Her gait is unsteady
and she fell 3 times. She has exquisite pain in her feet
when she steps on a sharp object. She also feels that
her lower limbs are weak.
Case 4 - PMH
Past Medical History:
• s/p cervical laminectomy in 1994 for severe spinal
stenosis
• s/p left 6th nerve palsy one year ago with resolution
• Stage 2 endometrial cancer in 2001, s/p surgery,
pelvic irradiation and chemotherapy (carboplatin /
paclitaxel)
• Hypothyroidism
Medications: diltiazem, l-thyroxine, ASA
Case 4 - Examination
Physical Examination:
• P=76/min, BP=142/80 mm Hg
• Neck ROM reduced in all directions
Neurologic Examination:
• Motor: Essentially normal
• Sensory: Absent vibration in hands and feet, 
position sense in toes, pin and temperature reduced
distal to mid forearms and calves and at umbilicus
• Coordination: ataxia with heel-to-shin testing
• Reflexes: MSR absent, plantar responses flexor
• Romberg unsteady, wide based gait
Case 4 – Laboratory
• NCS: Large fiber sensory demyelinating neuropathy
• CSF: 4 WBC, glucose 56 mg/dL, protein 116 mg/dL
Diagnosis?
Guillain-Barré Syndrome
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Large-fiber demyelinating neuropathy
Motor, sensory and autonomic nerves
Post-infectious and monophasic
Etiology: molecular mimicry
CSF: elevated protein, no cells
Treatment: plasmapheresis or IVIg
NO STEROIDS!